Published 4:00 am, Saturday, August 20, 2005

A salmonella germ may be part of a bacterial species responsible for thousands of deadly infections every year, but it can also be seen as a chassis loaded with useful gears and motors.

Tweak a genetic switch here, strip off a part there, and that germ might someday be converted into a powerful tool for doctors.

Like a cure for cancer, said Yale University scientist John Pawelek at the Life Engineering Symposium at UC San Francisco's Mission Bay campus Friday.

The next generation of genetic engineers is treating living things similar to the transformer toys they might have played with as kids. Viruses can become vehicles to deliver healthy genes into afflicted bodies, or the tools to construct computer components to exquisitely exact specifications.

So much more is now known about nature's toolbox -- genes and proteins -- that biologists can revamp existing organisms and even build new ones from scratch, said Christopher Voigt of UCSF. Voigt, an assistant professor of pharmaceutical chemistry, was the co-organizer of the two-day symposium on "synthetic biology" at Genentech Hall.

Genetic engineering began in the 1970s with the first efforts to splice just a few genes from a human or an animal into bacterial cells. Those cells could then produce useful proteins like insulin. Now scientists are taking that modular approach to life even further, combining genes from a range of varied microorganisms, plants and animals for a host of purposes. Such combinations might be used to boost production of a drug, create a means to deliver it to the right place in the body or make sure the drug will be active only when it will help, and not hurt.

Researchers like Voigt can now draw on a Massachusetts Institute of Technology "Registry of Standardized Biological Parts" and other lists to find the genetic sequences they need. And they're viewing those parts a lot like computer designers do. A genetic switch that makes a fish glow in the dark can also be used to release a therapeutic molecule.

But the manipulation of life forms also raises safety concerns and ethical questions.

The lab of UC Berkeley chemical engineering Professor David Schaffer is modifying a common virus as a potential vehicle for gene therapy. But Roger Brent, director of the Molecular Sciences Institute in Berkeley, noted that the same steps might be used to boost a virus' ability to cause disease.

Schaffer pointed out that the lab chose to experiment on a virus that is "a lousy pathogen" rather than something like the HIV virus. "We're very aware of the potential biosafety concerns," he said.

Voigt said improved methods to produce DNA sequences rapidly through chemical reactions have contributed greatly to the revolution in synthetic biology. Soon, researchers will no longer need to use gene-splicing methods to induce microorganisms to crank out DNA, he said.

"My students are going to learn a completely different type of biology than I learned," said Voigt, 28.

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